Merck Sharp & Dohme Corp. v. Actavis Labs. Fl, Inc.

Case Name: Merck Sharp & Dohme Corp. v. Actavis Labs. Fl, Inc., No. 15-cv-6075 (PGS) (DEA), 2017 U.S. Dist. LEXIS 164131 (D.N.J. Sept. 29, 2017) (Sheridan, J.) 

Drug Product and Patent(s)-in-Suit: Noxafil® (posaconazole); U.S. Patent No. 5,661,151 (“the ’151 patent”)

Nature of the Case and Issue(s) Presented: The ’151 patent was directed to the synthesis and clinical use of the antifungal compound posaconazole, which was used for treating or preventing fungal infections. A seven-day bench trial was held in July 2017. During trial, Actavis set forth the defense that filing of the ANDA application did not infringe the ’151 patent because the asserted claims 11 and 12 of the ’151 patent were invalid. Actavis asserted that: (i) claim 11 of the ’151 patent was invalid because it is inherently anticipated by the European Patent Application EP O 539 938 A 1 (“EP ’938”); and (ii) claim 12 was invalid because it was obvious to a POSA in view of the EP ’938 reference. Merck countered that Actavis had not met its burden of proof and that the EP ’938 reference was not prior art because the inventive concepts recited in claims 11 and 12 of the ’151 patent were invented on April 14, 1993, and diligently reduced to practice prior to or soon thereafter, thereby antedating the EP ’938 reference, published on May 5, 1993. The court found in favor of Merck.

Why Merck Prevailed:  For the court to determine that the claimed subject matter of claims 11 and 12 antedated EP ’938 reference, Merck had to show that the inventive concepts directed to posaconazole were (i) conceived prior to the publication date of EP ’938; and (ii) diligently reduced to practice soon thereafter. Actavis agreed that the structure of posaconazole was conceived on April 14, 1993. Thus, the court found that the chemical structure or formula of the chemical compound posaconazole was perceived on that date. But Actavis argued that Merck had presented no corroborated evidence that the inventors actually possessed an operative method of synthesizing posaconazole on April 14, 1993. In opposition, Merck contended that the inventors had extensive experience working on related antifungal compounds and that EP ’938 was a contemporaneous disclosure corroborating that the inventors knew how to make the azole core and the piperazine linker. The court found Merck’s arguments persuasive that on April 14, 1993, there was substantial corroborating evidence, such as contemporaneous documentation and testimony, to show that the inventors of the ’151 patent had an “operable route” to synthesizing posaconazole.

The actual reduction to practice of claim 11 took place on April 14, 1993, when inventors of the ’151 patent discovered the hydroxyl or OH group on the side chain of metabolite A. The Court found that the reduction to practice of posaconazole was envisioned on April 14, 1993, but some further testing and analysis was required on part of Schering’s scientists to determine and confirm which one of the six alcohols had adequate antifungal activity such that it could be commercially used. Although such further testing and analysis was not a requirement for showing actual reduction to practice, it was a prudent practice to confirm same through more in-depth analysis. Therefore, the subject matter recited in claim 11 was actually reduced to practice on April 14, 1993.

With respect to claim 12, the court found that one of the inventors was asked to synthesize the racemic mixture containing posaconazole and its corresponding stereoisomer. That experiment started on April 26, 1993 and was completed by May 26, 1993. With respect to synthesizing pure posaconazole compound, another inventor began the synthesis on June 30, 1993 and completed the synthesis on August 20, 1993. Since claim 11 , which was  incorporated in claim 12, applied to both a racemic mixture that contained posaconazole; and pure posaconazole, both dates applied as to the actual reduction to practice of the subject matter recited in claim 12.

Finally, the court addressed the issue of diligence. With respect to claim 11 , diligence was not an issue because posaconazole was conceived and simultaneously reduced to practice on April 14, 1993. With respect to claim 12, the court found that there were no gaps in the record that would allow one to question diligence on part of the inventors of the ’151 patent.